Study of the Expression of PD-l1 Expression among Primary Tumors and Nodal Metastases in Oral Squamous Cell Carcinoma of the Oral Cavity

Abstract

Event Abstract Back to Event Study of the Expression of PD-l1 Expression among Primary Tumors and Nodal Metastases in Oral Squamous Cell Carcinoma of the Oral Cavity Carlo Gervasoni1, Alessandro D'Aiuto2*, Lorenzo Azzi2, Marta Dani2, Lucia Tettamanti2 and Carlo Patriarca1 1 ASST Lariana, Unit of Maxillofacial Surgery, Italy 2 University of Insubria, Department of Medicine and Surgery, Italy Aim. Recent results with immunotherapy provided in many different metastatic neoplasias (melanoma, lung, kidney and bladder carcinoma) stimulate further investigation about the action of immune check-points, such as CTL-4, TIM 3, LAG-3 e PD-1/PD-L1, in other tumors. Among these tumours, those with high mutation load, such as head and neck cancer, are a distinguishing field of research. In oral squamous cell carcinoma, the checkpoint inhibitors have already undergone phase III study and there are preliminary PD-L1 expression data, which vary according to the grade and tumor stage. PD-L1 is an inhibitor ligand of PD-1 that is expressed on cytotoxic T lymphocytes. The drugs which have been studied can carry out an inhibitory action directly against PD-1 (nivolumab and pembrolizumab) or they can be directed against PD-L1 (atezolizumab and durvalumab). Materials and Methods. 16 OSCC of the oral cavity, p16 negative, T2-T4 and N1 staged, moderately differentiated (G2), underwent immunostaining with anti PD-L1 rabbit MoAb SP142, using VENTANA BenchMark Ultra platform with OptiView detection kit; anti-CD3 Ab and p16 VENTANA. Both primary tumours and nodal metastases were immunostained. Results were evaluated according to Roche PD-L1 (SP142) scoring system. CD3 immunostaing was conducted on primary tumor and on lymph node metastases in order to measure the interpretation of the facts. In particular, the expression of PD-L1 protein was explored both in the tumor compartment and in the lymph node metastasis, by the neoplastic cells (TC) and by the immune cells infiltrating the neoplasia (lymphocytes, macrophages, dendritic cells and granulocytes). Results. The whole group of 16 cases showed PD-L1 expression in perineoplastic immune cells, ranging from 1% to 50%, according to the scoring. No significant variations of expression (<10% of the difference), between primary tumor (T) and secondary nodal metastasis (N) were observed in all case but one. Conversely, 10 out of 16 cases (case 1, 2, 3, 7, 8, 9, 10, 12, 14, 15) showed no expression of PD-L1 on tumor cell (TC) (0%)both in primary tumor and nodal metastasis. The other 6 cases showed: case 4: T 0%, N 60%; case 5: T 80%, N 5%; case 6: T 70%, N 5%; case 11: T 50%, N 0%; case 13: T 30%, N 10%; case 16: T 40%, N 1%. Discussion. It is possible to conclude that the infiltrating tumour cells, in all their complexity, can be associated with a positive or negative prognosis according to various aspects: the histological and molecular form, the clinical and pathological stage, the surrounding microenvironment in which the neoplasia grows. These data, in addition to a new light on the relationship between the immune system and the neoplastic disease, provide useful information on the clinical management of cancer patients. Our study suggests that the plasticity of expression of PD-L1, observed in 37.5% of cases between the primary tumor and the lymph node metastasis, is an aspect to be considered in the treatment of oral squamous cell carcinoma of the oral cavity. However, the present study is characterized by a series of limitations: the number of cases examined is numerically limited and the results deserve to be found on a larger patient population; in fact, despite having selected by grade and stage the carcinomas of the HPV-oral cavity in order to reduce the studied variables, it is necessary to verify the reproducibility of the data in grades 3 and in M + neoplasms. Furthermore, the evaluation of the rabbit MoAb SP142 should be compared with evaluations of other MoAb anti PD-L1 (SP263, 22C3); in fact, the MoAb recognizes an intracellular domain of the molecule, thus it could explain the low tumor expression (CT), similarly to what is found in lung carcinomas and bladder.